ABSTRACT: The purpose of the Neuropathology Core and the Bryan Autopsy Program are to support the functions of the Clinical, Data Management, and Education Cores as well as our newly formed "Genomics Core," a privately supported collaborative initiative of the Bryan ADRC with the Institute of Genome Sciences and Policy (IGSP) to advance our Center's Genomic Medicine objectives. The Core provides diagnostic and tissue banking functions to support the Bryan ADRC and its myriad research projects. Since the focus of our Center has been historically on late onset AD, most of our demented Autopsy donors and our normal controls are very elderly. Mixed dementias and overlapping neurodegenerative syndromes are common. The Core has successfully developed standardized protocols for tissue processing, analysis, and diagnosis. Additionally, modern diagnostic criteria are continually updated and consistently applied by the Core Leader. A major function of this Core is to support cutting-edge research both directly and indirectly by providing tissue and other biological samples from well-characterized AD patients and from age-matched normal control subjects for research projects. Currently 1,047 fixed and frozen human brain specimens are available of which 128 are normal controls. The Core provides research material for trainees and stimulates innovative research related to clinical-pathological correlations in normal aging and neurodegenerative diseases and contributes to numerous genetic and epidemiologic studies. The Specific Aims of the Neuropathology Core are: 1. Provide diagnostic support for the Clinical Core, using standardized neuropathology assessment, by examining enrolled AD patients and genetic family members postmortem. 2. Expand and further develop brain banking functions for targeted populations: minority, normal controls, and subjects with Mild Cognitive Impairment (MCI). 3. Coordinate collection, storage and dissemination of high quality autopsy tissue, documented by quantitative RNA assessment, for research investigations. 4. Faciliate genomic medicine studies such as the envisioned gene expression studies with the IGSP and future studies to identify brain biomarkers related to transitions from MCI to dementia. 5. Continue our productive collaborations with the National Alzheimer's Coordinating Center (NACC) as well as with other program projects at Duke including the Udall Parkinson's Disease Research Center, the Center for Human Genetics, the National Academy of Sciences Twin Study, the Conte Center for the Neuroscience of Depression and the Cache County Utah Study of Memory in Aging.